Monoclonal antibody mediated biomarker discovery for alcohol-induced liver damage

单克隆抗体介导的酒精性肝损伤生物标志物的发现

基本信息

批准号：
7414655
负责人：
LAWRENCE DOUGLAS SNELL
金额：
$ 24.01万
依托单位：
LOHOCLA RESEARCH CORPORATION
依托单位国家：
美国
项目类别：
财政年份：
2008
资助国家：
美国
起止时间：
2008-09-30 至 2010-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7414655
关键词：
Affinity Affinity Chromatography Alcohol dependence Alcoholic Liver Diseases Alcoholic liver damage Alcohols Antibodies Antigens Biochemical Pathway Biological Biological Assay Biological Markers Biological Process Blood Boston Classification Clinical Clinical Research Collaborations Complex Control Groups Detection Development Diagnostic Disease Early Diagnosis Excision Gene Expression Gene Expression Profile Goals Hepatocyte Human Hybridomas Immunoassay Immunology Individual Institutes International Libraries Mass Chromatography Mass Spectrum Analysis Mediating Methodology Methods Molecular Monoclonal Antibodies Organ Outcome Participant Pathway interactions Patients Pattern Phage Display Pharmaceutical Preparations Phase Plasma Plasma Proteins Polymerase Chain Reaction Post-Translational Protein Processing Process Production Protein Microchips Proteins Proteome Proteomics Purpose Range Reagent Relative (related person)Reporting Research Sampling Science Screening Result Small Business Funding Mechanisms Small Business Innovation Research Grant Specificity Spectrometry Staging Statistically Significant Systems Biology Techniques Technology Testing Today Universities Validation alcohol exposure analytical method assay development base cost day interest liquid chromatography mass spectrometry liver biopsy new technology novel novel strategies programs protein expression prototype response success technology development three dimensional structure

项目摘要

DESCRIPTION (provided by applicant): The goal of this SBIR application is to demonstrate the feasibility of a global approach to screen for disease specific monoclonal antibodies (mAbs) to low level proteins for the discovery and validation of biomarkers of alcohol-induced liver damage. The technology will utilize a workflow that is essentially the reverse of that followed today, where antigens are first identified and then antibodies generated for potential biomarkers. In the present proposal, plasma proteome of alcohol-induced liver damage patients and a suitable control group will be screened against more than 1000 hybridomas for discriminating antibodies, seeking for at least 10 apparently disease specific discriminating biomarker mAbs. To demonstrate that the mAbs are to low level proteins, the antigens for at least 5 mAbs will be identified by affinity isolation and mass spectrometry. The level of these proteins in blood will also be determined or estimated. The suggested approach represents a novel method for biomarker discovery and validation, offering more than 10-fold greater sensitivity, as well as being 10-fold less expensive and many-fold higher throughput than present day LC/MS based approaches. Once feasibility of the approach has been demonstrated, the methodology will be ready for implementation on individual patient samples. Important to the success of this project is the collaboration of Biosystems International, a startup company with expertise in immunology and assay development, with the Barnett Institute at Northeastern University in Boston, MA, a research center with expertise in chromatography and mass spectrometry. A critical need today is the development of technology that can rapidly and cost effectively deliver disease specific antibodies for low level proteins in blood and that can be used to discover and validate biomarkers for the early detection of alcohol-induced liver damage. The goal of this program is to meet this need, and the reagents generated should be widely utilized for diagnostic purposes.

描述（由申请人提供）：该SBIR应用的目的是证明全球筛查疾病特异性单克隆抗体（MAB）的可行性，以发现和验证酒精诱导的肝脏损害的生物标志物。该技术将利用一个工作流，该工作流程基本上是随后的相反的，在该工作流程首先鉴定出抗原，然后为潜在的生物标志物生成抗体。在本提案中，将针对1000多个杂交瘤来筛选酒精诱导的肝损伤患者的血浆蛋白质组和合适的对照组，以区分抗体，以寻求至少10个明显的疾病特定于疾病的生物标志物mab。为了证明mAb是低水平蛋白的，将通过亲和力分离和质谱法鉴定至少5个mAb的抗原。这些血液中这些蛋白质的水平也将被确定或估计。建议的方法代表了一种新型的生物标志物发现和验证方法，其灵敏度高10倍以上，并且比当今基于LC/MS的方法更便宜10倍，并且吞吐量高10倍。一旦证明了该方法的可行性，该方法将准备好对个别患者样本实施。对于该项目的成功而言，重要的是生物系统国际公司的合作，这是一家具有免疫学和测定开发专业知识的初创公司，与马萨诸塞州波士顿东北大学的Barnett Institute，马萨诸塞州的Barnett Institute是一个研究中心，这是一个研究中心，具有色谱学和质谱法专业知识。当今的关键需求是技术的开发，可以快速和成本地赋予血液中低水平蛋白的特定疾病抗体，并且可用于发现和验证生物标志物，以早日检测到酒精引起的肝脏损害。该程序的目的是满足这一需求，应广泛用于诊断目的的试剂。